In-depth proteomic analyses of ovarian cancer cell line exosomes reveals differential enrichment of functional categories compared to the NCI 60 proteome
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Proteome
Exosome
Microvesicle
Biomarker Discovery
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Pathogenesis
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Exosomes, as nanoscale biological vesicles, have been shown to have great potential for biomedical applications. However, the low yield of exosomes limits their application. In this review, we focus on methods to increase exosome yield. Two main strategies are used to increase exosome production, one is based on genetic manipulation of the exosome biogenesis and release pathway, and the other is by pretreating parent cells, changing the culture method or adding different components to the medium. By applying these strategies, exosomes can be produced on a large scale to facilitate their practical application in the clinic.
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Cells release multiple, distinct forms of extracellular vesicles including structures known as microvesicles, which are known to alter the extracellular environment. Despite growing understanding of microvesicle biogenesis, function and contents, mechanisms regulating cargo delivery and enrichment remain largely unknown. Here we demonstrate that in amoeboid-like invasive tumour cell lines, the v-SNARE, VAMP3, regulates delivery of microvesicle cargo such as the membrane-type 1 matrix metalloprotease (MT1-MMP) to shedding microvesicles. MT1-MMP delivery to nascent microvesicles depends on the association of VAMP3 with the tetraspanin CD9 and facilitates the maintenance of amoeboid cell invasion. VAMP3-shRNA expression depletes shed vesicles of MT1-MMP and decreases cell invasiveness when embedded in cross-linked collagen matrices. Finally, we describe functionally similar microvesicles isolated from bodily fluids of ovarian cancer patients. Together these studies demonstrate the importance of microvesicle cargo sorting in matrix degradation and disease progression. Cells shed various types of vesicles differing in size and content. Here the authors show that cancer cells utilize VAMP3-mediated traffic to deliver MT1-MMP to surface microvesicles and facilitate amoeboid-like cell invasion, with VAMP3-containing vesicles also found in body fluids of cancer patients.
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Microvesicle biogenesis is a highly regulated process. Aberrant release of microvesicles from cancer cells have been associated with their invasiveness and prognosis. However, the mechanism of aberrant release remains poorly understood. Herein, we found that hepatocellular carcinoma cells shed more microvesicles than normal hepatocytes and miR-200a were shown to inhibit the release of microvesicles in hepatocellular carcinoma cells. Then, we confirmed that miR-200a might target Gelsolin and change cytoskeleton to regulate microvesicles secretion. Further miR-200a may inhibit the proliferation of adjacent cells by inhibiting the release of microvesicles. Collectively, our findings indicate that miR-200a regulated the microvesicle biogenesis involved in the hepatocellular carcinoma progression.
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Exosomes are generated by the multivesicular degradation of plasma membrane fusion, lysosomal, and extracellular release of intracellular vesicles. The exosome ranges from 30 to 150 nm in size. Exosomes are “bioactive vesicles” that promote intercellular communication. Exosomes contain a variety of biologically active substances packaged with proteins, lipids, and nucleic acids. After any microbe infection into the exosomes, the content of the exosomes changes and is released into the bloodstream. Such type of exosome content could be useful for basic research on exosome biology. Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis (Mtb). During the Mtb infection, the exosomes played an important role in the body’s infection and immune response by releasing several exosome components providing new ideas for diagnosis, prevention, and therapeutic treatment of Mtb infection. The detection of the low abundance of the Mtb numbers or secreted peptides in the serum of TB patients is not possible. The best way of findings for diagnosis and treatment of TB could be possible by the exploration of exosome content analysis through various useful technologies. The study and analysis of exosome content would produce a road map for the future early diagnosis, prognosis estimation, efficacy monitoring, research, and application for TB.
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